Analysis by ICP Atomic Emission Spectrometry in Accordance with the ICH Q3D

Guideline for Elemental Impurities

At the International Conference on Harmonisation of Technical Requirements for

Registration of Pharmaceuticals for Human Use (ICH), a variety of guidelines were
created and harmonized through three-party cooperation between Japan, the
United States and Europe. The guideline for elemental impurities is under review as
"ICH Q3D". In this guideline, the Permitted Daily Exposure (PDE) was established for
24 elemental impurities for which toxicity is a concern.

They include the "big four",

vLead (Pb)
vCadmium (Cd)
vMercury (Hg)
vArsenic (As),
as well as residual catalytic metals added intentionally in the synthesis of a drug
substance.
An ICP atomic emission spectrometer enables quick and easy analysis of multiple
elements.

Sample Pretreatment
An analysis was performed on an eye drop solution
and on tablets (daily intake: 1 tablet (0.2 g)). Nitric acid
and hydrochloric acid were added to the eye drop
sample, and it was diluted 5 times with pure water to
obtain the measurement solution.
Two of the tablets were dissolved with nitric acid and
hydrochloric acid using a microwave digestion system.
The sample was filled up 20mL for the measurement
solution (50 times dilution).

Analysis and Results

The Shimadzu ICPE-9820 multitype ICP atomic emission spectrometer was used as
the analysis system. The ICPE-9820 is equipped with an Echelle spectrometer and a
CCD detector, so the instrument is capable of simultaneously analyzing all elements
and all wavelengths.
This enables high-throughput measurements even when there are many target
elements and samples. In addition, the instrument is equipped with a mini torch and
a vacuum spectrometer, substantially reducing the running costs for gas in
comparison to other ICP instruments.

Analysis and Results

In this measurement, quantitative analysis and additive recovery tests were
performed on 24 elements cited in the ICH Q3D by the calibration curve method
internal standard method.
Table 1 shows the analysis results for the eye drop solution, and Table 2 shows the
analysis results for the tablets. Favorable results were obtained for the additive
recovery rates for both samples (columns marked with *1 in Tables 1 and 2). In
addition, the detection limits calculated from the concentrations in the samples
(columns marked with *2 in Tables 1 and 2) sufficiently satisfied the permitted
concentrations (columns marked with *3 in Tables 1 and 2).

PDE: Permitted Daily Exposure

PDE: Permitted Daily Exposure